Understanding Somatic Mutations
A somatic mutation is an alteration in DNA that occurs after conception and is not present within the germline. These mutations can occur in any cells of the body except germ cells (sperm and egg) and therefore are not passed on to children. 1
Key Characteristics of Somatic Mutations
Somatic mutations have several distinguishing features:
- Timing of occurrence: They develop after conception, unlike germline mutations which are present from conception
- Cell distribution: They affect only a portion of the body's cells, creating genetic mosaicism
- Heritability: They cannot be transmitted to offspring
- Clinical significance: They can contribute to disease development, particularly cancer
Somatic vs. Germline Mutations
Understanding the difference between somatic and germline mutations is crucial:
| Characteristic | Somatic Mutation | Germline Mutation |
|---|---|---|
| Origin | Occurs after conception | Present in reproductive cells |
| Distribution | Present in some body cells | Present in all body cells |
| Heritability | Not heritable | Can be passed to offspring |
| Detection | Requires tissue sampling | Can be detected in blood |
Clinical Implications of Somatic Mutations
Somatic mutations have significant clinical implications:
- Cancer development: They can drive tumor formation when they affect oncogenes or tumor suppressor genes
- Disease heterogeneity: Different somatic mutations within the same tumor can lead to treatment resistance
- Targeted therapies: Identification of specific somatic mutations can guide precision medicine approaches
Detection Methods
Several approaches can be used to identify somatic mutations:
- Tumor-normal sequencing: Comparing DNA from tumor tissue with DNA from normal tissue (usually blood) from the same individual
- Deep sequencing: Required to detect low-frequency somatic variants
- Bioinformatic analysis: Sophisticated algorithms to distinguish true somatic mutations from technical artifacts
Common Pitfalls in Somatic Mutation Interpretation
When evaluating somatic mutations, be aware of these potential pitfalls:
- Clonal hematopoiesis: Variants detected in blood may represent somatic mutations in hematopoietic lineages rather than true germline variants, especially in older patients or those who have received chemotherapy 1
- Sample contamination: Cross-contamination between samples can lead to false positive somatic mutation calls
- Technical artifacts: Sequencing errors can be misinterpreted as low-frequency somatic mutations
- Variant classification: Distinguishing driver mutations (that contribute to disease) from passenger mutations (that do not) remains challenging
Clinical Significance Assessment
The oncogenicity (pathogenicity in cancer context) of somatic variants should be carefully evaluated:
- Variants of uncertain significance (VUS) are common and should not guide routine clinical decisions
- Functional studies may be needed to determine the impact of novel variants
- Periodic review of variant classifications is necessary as new evidence emerges 1
Somatic mutations represent a fundamental aspect of cancer biology and aging, with important implications for diagnosis, prognosis, and treatment selection in clinical practice.